# Electronic cigarettes and cardiovascular outcomes: a systematic review and meta-analysis of Major Adverse Cardiovascular Events (MACE)

**Authors:** Suraa N. Al-Rubaye, Mohammedsadeq A. Shweliya, Mohamed Fawzi Hemida, Mohammad Bdair, Amr M. Abou Elezz, Mohamed Ashraf Shehab, Yara Abukhaled, Abdulrahman Raad Abdulkareem Al-waeli, Al-Tuaama Abdullah Zeyad Hameed, Abbas F. Abdul Hussein, Khadeeja Ali Hamzah, Mustafa Al-Jarshawi

PMC · DOI: 10.1186/s12889-026-26302-x · BMC Public Health · 2026-02-23

## TL;DR

E-cigarette use is linked to increased risks of heart-related issues like stroke and heart disease, but more research is needed to confirm long-term effects.

## Contribution

This study provides a comprehensive meta-analysis of e-cigarette use and cardiovascular risks, highlighting the need for further high-quality research.

## Key findings

- ENDS use is associated with a 1.57 higher odds of major adverse cardiovascular events.
- Dual users of e-cigarettes and traditional tobacco face the highest cardiovascular risk (OR = 2.21).
- Stroke risk is significantly elevated among ENDS users (OR = 1.62).

## Abstract

Electronic Nicotine Delivery Systems (ENDS), including e-cigarettes, are increasingly used worldwide, yet their association with major adverse cardiovascular outcomes remains inconclusive.

We conducted a systematic review and meta-analysis (PROSPERO: CRD420251026677) in accordance with PRISMA guidelines. PubMed, MEDLINE, Embase, and Scopus were searched up to May 10, 2025. Eligible studies included adolescents (13–18 years) and adults (≥ 19 years) using ENDS, reporting outcomes on any of the following: non-fatal myocardial infarction (MI), stroke, coronary artery disease (CAD), or cardiovascular mortality. The pooled odds ratios (ORs) were estimated using random-effects models and were considered the primary effect measures for assessing cardiovascular risk across exposure groups. Pooled outcome proportions were reported as secondary measures, reflecting the prevalence of outcomes within the ENDS-exposed population.

Twenty-six studies, comprising over 900,000 ENDS users, were analyzed. The meta-analyses showed significantly higher pooled odds of coronary heart disease (OR = 1.19, p < 0.0001), major adverse cardiovascular events (MACE) (OR = 1.57, p < 0.0001), and stroke (OR = 1.62, p < 0.01). The greatest risk was observed among dual users (OR = 2.21, p < 0.0001.), indicating additive cardiovascular harm associated with combined use. All outcomes demonstrated substantial heterogeneity between-study variability.

ENDS use is associated with potential cardiovascular harm, particularly regarding stroke and non-fatal MI; however, the overall findings are limited by substantial heterogeneity. Associations with CAD and mortality remain inconclusive due to data limitations. High-quality longitudinal studies are needed to clarify the long-term cardiovascular risks of ENDS, which could ultimately guide public health policies and initiatives.

The online version contains supplementary material available at 10.1186/s12889-026-26302-x.

## Linked entities

- **Diseases:** coronary artery disease (MONDO:0005010), stroke (MONDO:0005098), myocardial infarction (MONDO:0005068)

## Full-text entities

- **Genes:** EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}
- **Diseases:** Cardiovascular Mortality (MESH:D003643), Hypertension (MESH:D006973), Atherosclerotic Cardiovascular Disease (MESH:D050197), Adverse Cardiovascular Events (MESH:D002318), CKD (MESH:D012080), EC-MI (MESH:D009203), K-NHIS (MESH:D014813), cytotoxic (MESH:D064420), vascular injury (MESH:D057772), HF Heart failure (MESH:D006333), CAD (MESH:D003324), inflammation (MESH:D007249), ENDS (MESH:D014029), Coronary Heart Disease (MESH:D003327), endothelial dysfunction (MESH:D014652), Diabetes Mellitus (MESH:D003920), asthma (MESH:D001249), DM (MESH:D009223), Chronic Kidney Disease (MESH:D051436), COPD (MESH:D029424), Stroke (MESH:D020521)
- **Chemicals:** PM2.5 (-), acrolein (MESH:D000171), Nicotine (MESH:D009538), formaldehyde (MESH:D005557), oxygen (MESH:D010100), volatile organic compounds (MESH:D055549), aldehydes (MESH:D000447)
- **Species:** Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Cell lines:** NIHR — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_1306)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12927215/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12927215/full.md

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Source: https://tomesphere.com/paper/PMC12927215